On January 16, the U.S. Food and Drug Administration (FDA) granted traditional approval to the Bruton’s tyrosine kinase inhibitor acalabrutinib (Calquence) with bendamustine and rituximab for adults with previously untreated mantle cell lymphoma who are ineligible for autologous hematopoietic stem cell transplantation (HSCT).
The FDA also granted traditional approval to acalabrutinib as a single agent for adults with previously treated MCL. Acalabrutinib accelerated approval for this indication in 2017.
ECHO
Efficacy was evaluated in ECHO (ClinicalTrials.gov identifier NCT02972840), a randomized, double-blind, placebo-controlled, multicenter trial in 598 patients with untreated mantle cell lymphoma who were aged 65 years or older and not intended to receive HSCT. Patients were randomly assigned 1:1 to receive acalabrutinib plus bendamustine and rituximab (acalabrutinib plus BR) or placebo plus BR.
Efficacy was based on progression-free survival as assessed by an independent review committee. With a median follow-up of 49.8 months, progression-free survival was statistically significantly longer in the acalabrutinib arm (hazard ratio = 0.73, 95% confidence interval [CI] = 0.57–0.94, P = .016). The median progression-free survival was 66.4 months (95% CI = 55.1 months–not estimable) in the acalabrutinib plus BR arm and 49.6 months (95% CI = 36.0–64.1 months) in the placebo plus BR arm.
Serious adverse reactions occurred in 69% of patients treated with acalabrutinib plus BR, and fatal adverse reactions occurred in 12%. Serious adverse reactions reported in ≥ 2% of patients were pneumonia, COVID-19 infection, pyrexia, second primary malignancy, rash, febrile neutropenia, atrial fibrillation, sepsis, and anemia.
The recommended acalabrutinib dose is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review also used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review and Orphan Drug designation.
